RNA regulatory processes in RNA virus biology

Cross, Shaun T.; Michalski, Daniel; Miller, Megan R.; Wilusz, Jeffrey

doi:10.1002/wrna.1536

Cited by 36 publications

(34 citation statements)

References 225 publications

(294 reference statements)

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“…Database under NCBI accession number GSE135413. 1 Both authors contributed equally to this work. 2 Supported in part by National Science Foundation NRT Award 1450032 and by a National Science Foundation GRFP award.…”

Section: The Amino Acid Sequence Of This Protein Can Be Accessed Thromentioning

confidence: 99%

“…tant for maintaining cellular homeostasis. Therefore, it is not surprising that many aspects of post-transcriptional control are targeted and disrupted by RNA viruses during infection (1). RNA splicing, for instance, is a highly-regulated post-transcriptional process that relies on the proper localization of the spliceosome to avoid aberrant splicing events within the cell.…”

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confidence: 99%

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Zika virus noncoding sfRNAs sequester multiple host-derived RNA-binding proteins and modulate mRNA decay and splicing during infection

Michalski

Ontiveros

Russo

et al. 2019

Journal of Biological Chemistry

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Insect-borne flaviviruses produce a 300-500-base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5-3-exoribonuclease 1 (XRN1) via structures located in their 3 UTRs. In this study, we demonstrate that sfRNA production by Zika virus represses XRN1 analogous to what we have previously shown for other flaviviruses. Using protein-RNA reconstitution and a stringent RNA pulldown assay with human choriocarcinoma (JAR) cells, we demonstrate that the sfRNAs from both dengue type 2 and Zika viruses interact with a common set of 21 RNA-binding proteins that contribute to the regulation of post-transcriptional processes in the cell, including splicing, RNA stability, and translation. We found that four of these sfRNA-interacting host proteins, DEAD-box helicase 6 (DDX6) and enhancer of mRNA decapping 3 (EDC3) (two RNA decay factors), phosphorylated adaptor for RNA export (a regulator of the biogenesis of the splicing machinery), and apolipoprotein B mRNA-editing enzyme catalytic subunit 3C (APOBEC3C, a nucleic acid-editing deaminase), inherently restrict Zika virus infection. Furthermore, we demonstrate that the regulations of cellular mRNA decay and RNA splicing are compromised by Zika virus infection as well as by sfRNA alone. Collectively, these results reveal the large extent to which Zika virus-derived sfRNAs interact with cellular RNA-binding proteins and highlight the potential for widespread dysregulation of post-transcriptional control that likely limits the effective response of these cells to viral infection.

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Section: The Amino Acid Sequence Of This Protein Can Be Accessed Thromentioning

confidence: 99%

mentioning

confidence: 99%

Zika virus noncoding sfRNAs sequester multiple host-derived RNA-binding proteins and modulate mRNA decay and splicing during infection

Michalski

Ontiveros

Russo

et al. 2019

Journal of Biological Chemistry

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“…Moreover, the formation of sgRNAs is based on the discontinuous transcription leading to the leader–body fusion controlled by the RNA-dependent RNA polymerase and transcription-regulatory sequences (TRSs). TRSs, located at the 3′ end of the leader sequence (TRS-L) and preceding each viral gene (TRS-B), contain a conserved 6–7 nt core sequence and variable 5′ and 3′ flanking sequences 4 .…”

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N6-methyladenosine regulates RNA abundance of SARS-CoV-2

et al. 2021

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“…while avoiding cellular processing of viral RNA. One of the ways they achieve all this is through the use of RNA modifications ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

It’s the Little Things (in Viral RNA)

Potužník

Cahová

2020

mBio

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Chemical modifications of viral RNA are an integral part of the viral life cycle and are present in most classes of viruses. To date, more than 170 RNA modifications have been discovered in all types of cellular RNA. Only a few, however, have been found in viral RNA, and the function of most of these has yet to be elucidated. Those few we have discovered and whose functions we understand have a varied effect on each virus. They facilitate RNA export from the nucleus, aid in viral protein synthesis, recruit host enzymes, and even interact with the host immune machinery. The most common methods for their study are mass spectrometry and antibody assays linked to next-generation sequencing. However, given that the actual amount of modified RNA can be very small, it is important to pair meticulous scientific methodology with the appropriate detection methods and to interpret the results with a grain of salt. Once discovered, RNA modifications enhance our understanding of viruses and present a potential target in combating them. This review provides a summary of the currently known chemical modifications of viral RNA, the effects they have on viral machinery, and the methods used to detect them.

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RNA regulatory processes in RNA virus biology

Cited by 36 publications

References 225 publications

Zika virus noncoding sfRNAs sequester multiple host-derived RNA-binding proteins and modulate mRNA decay and splicing during infection

Zika virus noncoding sfRNAs sequester multiple host-derived RNA-binding proteins and modulate mRNA decay and splicing during infection

N6-methyladenosine regulates RNA abundance of SARS-CoV-2

It’s the Little Things (in Viral RNA)

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